NF-κB is a key regulator of inflammatory diseases, playing a central role in inflammation through the induction of proinflammatory gene transcription. Activation of NF-κB occurs via the nuclear translocation of cytoplasmic complexes in response to signals from pathogens or stress. The NF-κB/Rel family includes NF-κB1 (p50/p105), NF-κB2 (p52/p100), p65 (RelA), RelB, and c-Rel. These proteins can form homodimers or heterodimers, with the most prevalent activated form being a p50 or p52 heterodimer with p65. Studies in knockout mice have shown distinct roles for different NF-κB proteins in immune responses and disease. NF-κB activity is regulated by IκB proteins and the IκB kinase (IKK) complex. Phosphorylation of IκB by IKK leads to its ubiquitination and degradation, releasing NF-κB to translocate to the nucleus and induce gene transcription. IKK-β is essential for TNF-α and IL-1-induced NF-κB activation and is a potential target for therapies aimed at inhibiting proinflammatory gene expression. NF-κB plays a critical role in immune responses and inflammation, influencing adhesion molecules, apoptosis, and the production of proinflammatory cytokines. It is involved in various inflammatory diseases, including rheumatoid arthritis, asthma, and inflammatory bowel disease. NF-κB activation is also implicated in tissue-specific models of inflammation, such as glomerulonephritis and colitis. Therapeutic strategies targeting NF-κB include inhibitors of IKK, such as dominant-negative mutants and antisense oligonucleotides. These approaches have shown efficacy in animal models of inflammatory diseases, including arthritis and colitis. However, the potential for toxicity, such as liver apoptosis, must be considered. Selective targeting of specific NF-κB subunits or regulatory proteins may offer a more effective and safer approach to treating inflammatory diseases.NF-κB is a key regulator of inflammatory diseases, playing a central role in inflammation through the induction of proinflammatory gene transcription. Activation of NF-κB occurs via the nuclear translocation of cytoplasmic complexes in response to signals from pathogens or stress. The NF-κB/Rel family includes NF-κB1 (p50/p105), NF-κB2 (p52/p100), p65 (RelA), RelB, and c-Rel. These proteins can form homodimers or heterodimers, with the most prevalent activated form being a p50 or p52 heterodimer with p65. Studies in knockout mice have shown distinct roles for different NF-κB proteins in immune responses and disease. NF-κB activity is regulated by IκB proteins and the IκB kinase (IKK) complex. Phosphorylation of IκB by IKK leads to its ubiquitination and degradation, releasing NF-κB to translocate to the nucleus and induce gene transcription. IKK-β is essential for TNF-α and IL-1-induced NF-κB activation and is a potential target for therapies aimed at inhibiting proinflammatory gene expression. NF-κB plays a critical role in immune responses and inflammation, influencing adhesion molecules, apoptosis, and the production of proinflammatory cytokines. It is involved in various inflammatory diseases, including rheumatoid arthritis, asthma, and inflammatory bowel disease. NF-κB activation is also implicated in tissue-specific models of inflammation, such as glomerulonephritis and colitis. Therapeutic strategies targeting NF-κB include inhibitors of IKK, such as dominant-negative mutants and antisense oligonucleotides. These approaches have shown efficacy in animal models of inflammatory diseases, including arthritis and colitis. However, the potential for toxicity, such as liver apoptosis, must be considered. Selective targeting of specific NF-κB subunits or regulatory proteins may offer a more effective and safer approach to treating inflammatory diseases.